Influence of PCB153 on oxidative DNA damage and DNA repair-related gene expression induced by PBDE-47 in human neuroblastoma cells in vitro.
We studied the relationship between 2,2,4,4-tetrabromodiphenyl ether (PBDE-47) and oxidative DNA damage as well as the mode of interaction between PBDE-47 and 2,2,4,4,5,5-hexachlorobiphenyl (PCB153) by incubating SH-SY5Y cells in four doses of PBDE-47 (0, 1, 5, 10 microM) and/or 5 microM PCB153 and 100 microM NAC (N-acetylcysteine) for 24 h. Results showed that reactive oxygen species (ROS) production in the 5 microM PBDE-47 + PCB153 and 10 microM PBDE-47 + PCB153 groups were significantly higher than that of the control group (p < 0.05). DNA strand breakage and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were significantly increased in the 10 microM PBDE-47, 5 microM PBDE-47 + PCB153, and 10 microM PBDE-47 + PCB153 groups compared with the control (p < 0.05). Furthermore, ROS formation and DNA strand breakage were dramatically increased in the 5 microM PBDE-47 + PCB153 and 10 microM PBDE-47 + PCB153 groups compared with the corresponding PBDE-47 only group and the PCB153 group (p< 0.05). The level of 8-OHdG was significantly increased in the 10 microM PBDE-47 + PCB153 group compared with the corresponding PBDE-47 only group and the PCB153 group (p < 0.05). The PBDE-47 group coincubated with NAC decreased the ROS level and ameliorated PBDE-47-mediated DNA damage. The mRNA expression levels of X-ray repair cross-complementing gene 1 (Xrcc1) were significantly decreased in the 10 microM PBDE-47, 5 microM PBDE-47 + PCB153, and 10 microM PBDE-47 + PCB153 groups, whereas X-ray repair cross-complementing gene 3 (Xrcc3) were significantly increased in the 10 microM PBDE-47 and 10 microM PBDE-47 + PCB153 groups compared with the control (p < 0.05). The PBDE-47 groups coincubated with NAC, however, considerably increased Xrcc1 while decreasing Xrcc3 mRNA expression (p < 0.05). These results indicate that PBDE-47 induced oxidative DNA damage and that PBDE-47 combined with PCB153 may increase such effects in SH-SY5Y cells in vitro. Furthermore, our results suggest that oxidative stress is responsible for DNA damage induced by PBDE-47.
Gao
Ping
P
Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.
He
Ping
P
Wang
Aiguo
A
Xia
Tao
T
Xu
Bayi
B
Xu
Zhixia
Z
Niu
Qiang
Q
Guo
Lijuan
L
Chen
Xuemin
X
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000111:Acetylcysteine / Q000378:metabolism; D045744:Cell Line, Tumor; D053960:DNA Breaks / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D055768:Halogenated Diphenyl Ethers / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D055768:Halogenated Diphenyl Ethers; D017382:Reactive Oxygen Species; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C511295:2,2',4,4'-tetrabromodiphenyl ether; D000080242:8-Hydroxy-2'-Deoxyguanosine; D011078:Polychlorinated Biphenyls; D003849:Deoxyguanosine; D000111:Acetylcysteine; C014024:2,4,5,2',4',5'-hexachlorobiphenyl